Ischemic heart disease is typically the result of an insufficient supply of blood to the heart muscle or myocardium often caused by constriction or obstruction of the blood vessels. For example, progressive artherosclerosis with increasing occlusion of coronary arteries leads to a reduction in coronary blood flow. Hypoperfusion, vasospasm and thrombosis can lead to a further decrease in blood flow.
Myocardial infarction (MI) occurs when the blood supply to the heart is suddenly interrupted which results in insufficient oxygen and other nutrients.
Systemic delivery of drugs for the treatment of myocardial infarction has been relatively effective. However, a significant portion of the population ultimately develops heart failure post-MI. Remodeling of the heart muscle such as the right or left ventricle, post-MI, is a significant component of the progression to heart failure due to uneven stress and strain distribution of the left ventricle post-MI.
Principle components of the remodeling event include myocyte death, edema and inflammation, followed by fibroblast infiltration and collagen deposition, and finally scar formation. The principle component of scar tissue is collagen.
Myocyte loss is a major etiologic factor of wall thinning and chamber dilation that may ultimately lead to progression of cardiomyopathy, a heart disease wherein the heart muscle, typically the left ventricle, is abnormally enlarged, thickened and/or stiffened, which can result in impairment of the heart muscle's ability to pump blood.
The controlled local delivery of drugs has become increasingly desirable because higher doses can be maintained locally and the delivery of drugs directly to diseased tissue can be sustained over a longer period of time, can minimize side effects and is more effective against destructive myocardial remodeling post-MI.